Tommaso Giani, PhD e-mail: [email protected] Tel. +390577233855 P0723 Ac#vity of ceobiprole and comparators against hospital-acquired pneumonia pathogens from Italy, January-May 2016 Tommaso Giani1, Alberto Antonelli2, Marco Coppi2, Olga Lorenza Colavecchio2, Viola Conte1, Anne Santerre Henriksen4, Gian Maria Rossolini2, 3 1 Department of Medical Biotechnologies, University of Siena, Siena, Italy; 2 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 3 Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy; 4 Basilea PharmaceuQca Int. Ltd, Basel, Switzerland Introduc#on and purpose Results Table 1. Percentage of suscepQble (S) isolates to ce]obiprole and comparators DI among the most frequently isolated Gram- negaves isolated from HAP in Italy. • Hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP) are among the most common • A total of 313 isolates of Gram-negave and Gram-posiQve isolates were collected CBP FEP CAZ PTZ MEM ERT CIP COL TIG GEN infecQons treated in the hospital seng 1 • Of all the isolates, the most common species were P. aeruginosa (n=106, 34%), Klebsiella pneumoniae (n=63, 20%), S. K. pneumoniae (n=63) % S 35 38 36 40 62 57 38 78 79 63 • Successful outcomes of such infecQons depend on rapid and adequate empirical anQbioQc therapy that could be aureus (n=42, 13%) and Escherichia coli (n=26, 8%) E. coli (n=26) % S 58 58 61 77 96 96 46 100 100 77 challenging especially in sengs, such as Italy, characterized by a high proporQon of mulQ-drug resistant isolates • Overall 65 MRSA strains were collected from 12/13 centers • Ce]obiprole is a 5th-generaon cephalosporin with an expanded-spectrum and potent acQvity against Gram-posiQve 100 • Considering the most frequently isolated Enterobacteriaceae, ce]obiprole showed an acQvity similar to ce]azidime and and -negave bacteria. It is approved for markeQng in various European and non-European countries for the cefepime, being acQve against 35% and 58% of K. pneumoniae and E. coli, respecvely (Table 1) 80 treatment of HAP (excluding venQlator-associated pneumonia) and CAP in adults 2 • MIC50 and MIC90 values of ce]obiprole for P. aeruginosa were 8 mg/L and >16 mg/L, respecQvely. Cumulave MIC • Ce]obiprole has in vitro acQvity against methicillin-resistant Staphylococcus aureus (MRSA) and other common distribuQon indicated that ce]obiprole showed a similar trend to ce]azidime (Figure 2) 60 PTZ pathogens in pneumonia, e.g. Enterobacteriaceae not expressing extended spectrum β-lactamases (ESBLs) or • All methicillin-suscepQble S. aureus (MSSA) isolates were suscepQble to ce]obiprole (Table 2A) CAZ carbapenemase and non-carbapenemase producing Pseudomonas aeruginosa 3 40 P. aeruginosa • All MRSA isolates were suscepQble to vancomycin, teicoplanin and linezolid; ce]obiprole had acQvity against 95.3% of these inhibited CBP • The objecQve of this study was to invesQgate the in vitro acQvity of ce]obiprole and comparators against a collecQon MEM isolates (Table 2B) 20 of clinical isolates putavely responsible for HAP, representave of the contemporary Italian epidemiology of % 0 2 Figure 1. Geographical Methods distribuon of parcipang 0.5 1 2 4 8 16 >16 4 centres. Centers were as follow: MIC (mg/L) 1 Bacterial strains 1. Lecco; 2. Bolzano;3 Arezzo; 4. Figure 2. Cumulave MIC distribuQon for P. aeruginosa isolates against anQ-pseudomonas β-lactams 13 • 13 different centers were involved in the study (locaon of the satellite centers is reported in Figure 1). During the Udine; 5. Florence; 6. Perugia; 7. 10 Ancona; 8. Rome; 9. Foggia;10. study period (January 1 – May 31, 2016), all satellite centers were asked to collect up to 25 consecuQve, non- Torino;11. Cesena; 12. Catania; 13. Milan. Table 2. SuscepQbility profiles and MIC50 and MIC90 of all MSSA (A) and MRSA (B) isolates against ce]obiprole and comparators. MIC values are in mg/L. replicate clinical isolates, of all species, putavely responsible of HAP. During the same period, the collecQng centers 11 A B also collected all MRSA isolates from HAP 5 7 TOT=42 CBP CLI ERY LEV LNZ OX TEC TGC SXT VA TOT=65 CBP CLI ERY LEV LNZ TEC TGC SXT VA • All isolates were sent to the reference laboratory for confirmaon of species idenQficaon and minimum inhibitory 3 6 concentraon (MIC) tesQng of ceobiprole and comparator molecules MIC50 0.25 0.12 0,5 0.25 2 0.5 0.5 0.25 ≤0.06 1 MIC50 1 0.12 >1 16 2 0,5 0.25 ≤0.06 1 Isolate idenficaon and anmicrobial suscepbility tesng 8 MIC90 0.5 0.12 >1 0.5 4 1 1 0.25 0.25 1 MIC90 2 >1 >1 >16 4 1 0.5 0.12 1 • IdenQficaon of all collected isolates was performed using the MALDI-TOF Vitek-MS system (bioMérieux, Marcy 9 L’Etoile, France). To test the acQvity of ce]obiprole and comparators all collected isolates were subjected to MIC %S 100 95.2 71.4 95.2 100 92.8 100 100 100 100 %S 95.3 86.1 16.2 13.8 100 100 100 98.5 100 tesQng by reference broth microdiluQon procedure using custom plates (Thermo Fisher ScienQfic) 4 • MIC results were interpreted as suscepQble, intermediate and resistant according to EUCAST breakpoints according CBP: ceobiprole; CLI: clindamycin; ERY: erythromycin; LEV: levofloxacin; OX: oxacillin; TEC: teicoplanin; TGC: gecycline; SXT: trimethoprim/sulphametoxazole; VA: vancomicin; FEP: cefepime; CAZ: ce]azidime; PTZ: piperacillin-tazobactam; MEM: meropenem; ERT: ertapenem; CIP: ciprofloxacin; COL: colisQn; GEN: gentamicin (hp://www.eucast.org/clinical_breakpoints). The MRSA phenotype was confirmed by cefoxiQn broth microdiluQon and, in case of discrepancy between central-laboratory and collecQng-center results, a cefoxiQn screen test using Conclusions disk-diffusion, following EUCAST rules, was performed • Ce]obiprole showed a broad spectrum of acQvity against a collecQon of contemporary Gram-negave and Gram-posiQve HAP clinical isolates 12 from Italy References • A high prevalence of both ESBL- and carbapenemase-producing Enterobacteriaceae was observed, affecQng suscepQbility against all 1 Torres A, et al. Treatment guidelines and outcomes of hospital-acquired and venQlator-associated pneumonia. Clin. Infect. Dis. 2010 2 Scheeren TW. Ceobiprole medocaril in the treatment of hospital-acquired pneumonia. Futur Microbiol. 2015 anQbioQcs tested 3 Farrel, DJ, et al. Ce]obiprole acQvity against over 60,000 clinical bacterial pathogens isolated in Europe, Turkey, and Israel from 2005 to 2010. AnQmicrob. Agents Chemother. 2014 Acknowledgements • This study confirmed that ce]obiprole could be a valid therapeuQc opQon in case of HAP caused by MRSA. The MRSA included in this study 4 Clinical Laboratory Standards InsQtute. Methods for diluon anQmicrobial suscepQbility. Tests for bacteria that grow aerobically; Approved Funding for this researh was provided by Basilea PharmaceuQca Internaonal Ltd, Basel, will be subjected to Whole Genome Sequencing in order to assess their clonality, resistome and geneQc background of mecA gene standards. 10th ed. CLSI document M07-A10. Wayne, PA: CLSI; 2015 Switzerland. ASH is an employee of Basilea. .